Relationship and contentRelationship betweenoccupationsandasbestos-fibre contentof thelungs Merseyside hospitals, and 45 patients were from other parts of north-west England. Normal

Thorax, 1977, 32, 377-386

Relationship between occupations and asbestos-fibre content of the lungs in patients with pleuralmesothelioma, lung cancer, and other diseasesF. WHITWELL, JEAN SCOTT, AND MYRA GRIMSHAW

From the Department of Pathology, Broadgreen Hospital, Liverpool 14

Whitwell, F., Scott, Jean, and Grimshaw, Myra (1977). Thorax, 32, 377-386. Relationshipbetween occupations and asbestos-fibre content of the lungs in patients with pleuralmesothelioma, lung cancer, and other diseases. The light-visible asbestos-fibre content of 300lung specimens has been measured using a potash-digestion and phase-contrast microscopytechnique, and the results have been correlated with the occupations of the patients.Among 100 pleural mesothelioma specimens were 88 where the patients had been exposed to

asbestos, and in 73 of these (83%) the lung tissue contained over 100 000 asbestos fibres pergram of dried lung, and only one specimen showed less than 20 000 fibres per gram. Whenasbestosis was present, the lungs nearly always showed over 3 million fibres per gram.

In 100 control lungs (those without industrial disease or lung cancer) there were less than20 000 fibres per gram of dried lung in 71% of specimens. Lungs from 100 patients with lungcancer but no industrial disease contained less than 20 000 fibres per gram of dried lung in80% of cases. Patients with parietal pleural plaques nearly all had over 20 000 fibres per gramin their lungs.The number of asbestos fibres found in the lungs was closely related to the occupations of the

patients but not to their home environment. Patients who had lived near likely sources ofatmospheric asbestos pollution did not have higher asbestos fibre counts than the rest of thepatients.

It is concluded that there is a definite dose relationship between asbestos exposure andmesothelioma formation but that' 'sub-asbestosis' levels of asbestos exposure do not contributeto the formation of lung cancer in those not subjected to industrial asbestos exposure.

In 1960 a link between pleural mesothelioma andprevious asbestos exposure was described byWagner et al., the degree of exposure usually hav-ing been insufficient to cause asbestosis, and ac-quired more often in the home than in theindustrial environment. Shortly afterwardsThomson et al. (1963) reported that asbestosbodies were present in about 30O/% of adult lungsexamined at necropsy from patients who had hadno known industrial exposure.Both these findings have been confirmed many

times from different countries, with only slightmodification. The asbestos exposure of patientswith asbestos-induced mesotheliomas has usuallycome from industrial exposure, though a few cases

have been reported where the only known asbestoshazard had been the home environment, con-taminated by nearby industrial plants, workclothes, or even household articles containingasbestos (Newhouse and Thompson, 1965; Green-berg and Davies, 1974). The percentage of urbanlungs containing asbestos bodies has been foundto be much higher than in the original seriesexamined, sometimes over 90% (Utidjian et al.,1968), largely due to more elaborate methods ofextracting asbestos bodies from lungs.Another possible effect of 'sub-asbestosis' levels

of asbestos exposure is an enhancement of thecarcinogenic effect of cigarette smoking in induc-ing lung cancer. as suggested by Selikoff et al.

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(1973) from surveys of large numbers of insulationworkers in the United States. Their view has beensupported by Warnock and Churg (1975), whofound that in a community free from industrialasbestos exposure lung cancer patients had signifi-cantly more asbestos bodies in their lungs thanwere found in control patients without lungcancer from the same community.The shortcomings of many studies have been

the inadequacy of occupational histories ofpatients, the crude methods of assessing from thelungs the degree of previous asbestos exposure,

and often the absence of postmortem confirma-tion of the nature of tumours. The early work on

the link between asbestos exposure and meso-

thelioma naturally relied upon retrospectivestudies in which case records contained little in-formation about occupation and often little or

no lung tissue had been preserved. A similardearth of histological evidence confuses the pos-

sible link between 'sub-asbestosis' asbestosexposure and lung cancer.

The present study is an analysis of the asbestos-fibre content of the lungs from 100 pleural meso-thelioma patients, 100 control patients (who haddied from conditions other than industrial lungdisease or lung cancer), and 100 lung cancerpatients who did not have industrial lung disease.In nearly all patients occupational histories havebeen taken in some detail, and in many cases

residential histories have also been obtained. Thework began as an attempt to find out whichpleural mesotheliomas were induced by asbestosand which were spontaneous tumours, and waslater extended to study a normal control seriesand patients with lung cancer.

Methods of the investigation

HISTORY TAKING

Mesothelioma seriesOver half the patients died in Merseyside hospitals,many in Broadgreen Hospital. Often those whodied in other Merseyside hospitals had previouslybeen investigated in Broadgreen Hospital. Inthese cases detailed occupational, residential, andfamily histories were taken covering possibleasbestos exposure during the whole of thepatients' lives. Though these were usually easilyobtained, cases occurred where the exposure hadbeen for only a few months over half a centuryago, likely to be overlooked by the patients unlessquestioned closely, and often quite unknown torelatives. Considerable patience and a knowledgeof the past uses of asbestos were needed in obtain-

F. Whitwell, Jean Scott, and Myra Grimshaw

ing some histories, but unless the information isobtained from the patients it becomes lost as therelevant asbestos exposure often happened beforesurviving relatives were born.For other patients in this series similar informa-

tion was sought from patients or their relatives bythe staff of the hospitals where the patients weretreated, or by the medical staff of the ManchesterPneumoconiosis Medical Panel.

Normal control seriesThe usual inadequacies of occupational histories inhospital case-records made this the most difficultseries to collect, and it proved difficult to arrangeinterviews with relatives after patients had died.Although there are over 600 postmortem examina-tions per year in the hospital it took about sixmonths to collect the first 50 cases with adequateoccupational histories. The problem was solvedwith the help of the Merseyside coroner, whopermitted his staff to complete a questionnaireabout jobs and residences for each patient wheninterviewing relatives for other purposes. Thesecond half of this series therefore consists ofthose brought dead into the hospital.

Lung cancer seriesThese patients provided the fullest histories asthey were all patients in the CardiothoracicSurgical Centre at Broadgreen Hospital beingtreated by pneumonectomy or lobectomy for lungcancer. One week after operation they were inter-viewed by one of us (MG) when notes were madeof all occupations, residences, hobbies, occupa-tions of close relatives, and smoking histories. Inorder not to alarm the patients the interviews werecarried out with all surgical patients, not just thosewith lung cancer. The only patients not inter-viewed after pneumonectomy or lobectomy werethose who died early in the postoperative period,and a few who were quickly transferred to anotherhospital because their lesions proved to betuberculous.

MATERIAL OF THE STUDY

Mesothelioma seriesThe series comprised 100 consecutive pleuralmesothelioma lung specimens, obtained atnecropsy, which had been submitted to the Man-chester Pneumoconiosis Medical Panel by coronersin north-west England between 1973 and 1976.The specimens had been fixed in formalin, in mostcases by its injection into the bronchial tree toinflate the lungs. Eighteen patients had died inBroadgreen Hospital, 37 patients were from other



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Relationship between occupations and asbestos-fibre content of the lungs

Merseyside hospitals, and 45 patients were fromother parts of north-west England.

Normal control seriesThe normal control series consisted of BroadgreenHospital patients in 1975 and 1976 who wereover 20 years of age at necropsy, had neitherindustrial lung disease nor lung cancer, and hada lower lobe of lung free of pneumonia or in-farction. This lobe was then inflated with formolsaline through the bronchial tree. Where an ade-quate occupational history had been obtained thelobe was used for asbestos-fibre analysis. FromAugust 1976 only lungs from coroner's necropsieswere used. Apart from being selected by theavailability of an occupational history, and latercases being those referred from the coroner, thespecimens formed a consecutive series until 80had been examined. From that time only lobesfrom male patients between 50 years and 70 yearsof age were used, in order to avoid excessive im-balance of the sex and age distribution in thethree series (Table 1).

Lung cancer seriesThis consisted of 100 lungs or lobes removedsurgically at Broadgreen Hospital in 1975 and1976 because they had contained lung cancers.They were consecutive specimens, except for theomission of some specimens with insufficientnormal lung tissue due to the size of the tumouror because of secondary lung changes. Also, caseswere omitted when the patient died before an

adequate history had been obtained. The speci-mens were fixed either in the operating theatreby formalin injection through the bronchial tree,or later in the pathology department.

TISSUE STUDIES OF EFFECTS OF ASBESTOS EXPOSURE

In the mesothelioma and normal control seriesthe parietal pleura was examined at necropsy forcollagenous plaques. The necropsy reports ofpathologists submitting mesothelioma specimensto the Pneumoconiosis Medical Panel often com-

mented on the presence or absence of pleuralplaques. In the lung cancer series the surgeons

usually did not see or comment on pleural plaques,though these were often found at necropsy inpatients who had died after operation.

In all cases the lungs were examined macro-scopically for asbestosis and microscopically forasbestosis and asbestos bodies. In addition toroutine sections, thick unstained sections wereexamined in many specimens.

In the mesothelioma series lung juice smearswere prepared using a method already described(Whitwell and Rawcliffe, 1971), and the numbersof asbestos bodies on slides were counted. Whenunfixed lung tissue was used in making thesepreparations the results provided a roughly quan-titative assessment of previous asbestos exposure.When the preparations had to be made from fixedlung tissues far fewer asbestos bodies were seen

and it was not possible to correlate the findingswith previous asbestos exposure.As most of the specimens examined were al-

ready fixed, a more reliable indicator of asbestosexposure was sought.

Asbestos-fibre counts on lung tissueBecause of the limitations of the previous tech-nique, it was decided to count the asbestos fibres,coated and uncoated, which could be extractedfrom lung tissue. Ideally, one would wish to countall fibres, including those too fine to be seen bylight microscopy, but this was beyond our re-

sources. However, it has been stated that theratio of light-visible fibres to total fibres is fairlyconstant (Timbrell, 1973; Ashcroft and Hepples-ton, 1973) so it was thought worth while to countthe light-visible fibres.

In 1968 Gold evolved a method of countingasbestos fibres in lung tissue by macerating a

known weight of dried lung tissue in potash, wash-ing the digestion mixture three times in distilledwater, and counting the fibres in an aliquot of thesuspension in a Fuchs-Rosenthal chamber. Weused this method in 1972 but found few fibres, andthe results were difficult to reproduce with con-

sistency. Ashcroft and Heppleston (1973) improvedthe method, largely by reducing the washings ofthe deposit to one, using wet lung tissue with

Table 1 Sex and age distribution of the three series

Series Sex Age (years)

M F 20-29 30-39 40-49 50-59 60-69 70-79 80-89

Mesothelioma 86 14 1 3 5 29 40 22 0Control 72 28 3 5 12 25 27 20 8Lung cancer 78 22 0 1 7 29 55 8 0

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calculation of the equivalent dry weight, andusing phase-contrast microscopy. These workerscould see finer fibres and also more fibres thanwere seen by Gold's method, counting fibres ofabout 3 , in length or 0 4 ,u diameter, whereas byGold's method it was difficult to see fibres of lessthan about 12 u in length.

Since the end of 1972, and for the whole ofthe present investigations, we have followed themethod of Ashcroft and Heppleston, except thatwe count only fibres over 6 p, in length, as smallerfibres can be confused with bacteria. Coated anduncoated fibres are counted together. Althoughthe method sounds crude, the results are repro-ducible with a coefficient of variance of about 7%(Table 2). More variation can arise through theselection of lung tissue than in the actual count-ing, and with all specimens we have used the baseof the more normal lower lobe, just above thediaphragmatic pleural membrane, except withupper lobe carcinoma specimens where we haveused the lower part of the upper lobe. The fibrescounted are nearly always amphibole asbestos, asit is very difficult to see the finer crysotile fibres.Before using this test routinely familiarisation

with the appearances of different asbestos fibres indigestion mixtures in counting chambers wasgained by studying digested normal lung tissueswhich had been fixed with formol saline contain-ing UICC asbestos samples.

In the following text, where numbers of fibresare mentioned, the figure refers to fibres per gramdried lung, usually from the base of a lower lobe.

Table 2mixture

Ten asbestos-fibre counts on one digestion

Count Number counted Fibres per gram dried lung

1 175 328 0002 168 315 0003 159 298 0004 145 272 0005 162 304 0006 160 300 0007 139 261 0008 146 274 0009 157 295 00010 161 302 000

Mean 295 000.SD 20500.Coeff of variance 6 95%.

Results

MESOTHELIOMA SERIESThe range of asbestos fibres per gram of dried lungfound in the base of the lower lobe in the speci-mens ranged from nil to 70 million, as shown inFig. 1, which also indicates the relevant occupa-tion of each patient, except for five patients whosehistory was unknown. When patients had followedmore than one occupation that carried an asbestos

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exposure risk the more hazardous one was usedin the classification; for example, several shipyardworkers had previously been in the Navy.There were 88 cases with a history of asbestos

exposure, and in all but one of these the lungsshowed over 20000 fibres. The one patient withprobable asbestos exposure and fewer fibres was aman aged 79 years who, between the ages of 15and 31 years, had been a plumber in a shipyard,afterwards becoming an office clerk. No pleuralplaques were found at necropsy. Seventy-threepatients (83%) with a history of asbestos exposurehad over 100 000 fibres, and in 23 of these patients(26%) there was some histological asbestosis. Mostof the lungs showing asbestosis contained over 3million asbestos fibres, and the numbers ofasbestos fibres present corresponded roughly withthe degree of asbestosis (Table 3). Asbestosis waspresent in over half the patients who had workedin asbestos factories or gas-mask factories but inless than one-fifth of patients who had worked inshipyards or sack-repair factories.

Table 3 Asbestos fibre counts in millions per gramdried lung in 23 of the 100 mesotheliomas whichshowed some asbestosis

Asbestosis

Mild Moderate Severe

1-0 2 0 6 51-4 4-6 183-1 5 5 233-3 8-0 463-3 10 576-0 17 708-0 24

23 4423

Arithmetic mean 8 14 37Geometric mean 4-7 9-6 28

The patients who had worked in gas-mask andsack-repair factories form an interesting group,

being among the few who had worked for onlya brief period in a hazardous environment, usuallyduring the first or second world war, and had

otherwise been housewives. The residual asbestosfibre count found in some of these patients' lungsis given in Table 4, showing that 60 years afteran asbestos exposure of less than one year's dura-tion which had been insufficient to cause asbes-tosis, the lung retained over half a million asbestosfibres. The gas-mask case listed in Fig. 1 withbetween 50 000 and 100 000 fibres is the only homeenvironment asbestos-induced mesothelioma inthe series, being the son of a worker from a gas-mask factory where the workers took crocidolitehome to pack into canisters.The seven patients with no credible history of

asbestos exposure were three housewives, a

farmer, a fireman, a clerk, and a crankshaft fitter.Pleural plaques were not noted in any of theirnecropsy reports, all had under 40 000 asbestosfibres, six being less than 20 000 fibres, and no

fibres were seen in two cases. These cases must bespontaneous pleural mesotheliomas.

NORMAL CONTROL SERIES

The commonest causes of death in this serieswere ischaemic heart disease in 48%. malignancyin 10%, and pulmonary embolus in 7%. The highfrequency of heart disease was due to the inclusionof many coroner's cases.

No asbestosis or excess asbestos bodies were

found in the routine histological studies.Bilateral pleural plaques were seen in 21 cases,

all male.The asbestos-fibre counts of this series are

shown in Fig. 2, 57% having less than 10 000fibres and 71% having less than 20 000 fibres.Thirty-five per cent of male patients, but only14% of female patients, had over 20 000 fibres.Nearly all the patients had lived the greater part

of their lives in Liverpool but it was not possibleto assess any influence of home environment on

the asbestos-fibre levels. However, the jobs of the10 patients with the highest and lowest counts inthe series (Table 5) suggest that the patients' workis largely responsible for the amount of asbestosin the lungs. The 10 patients with the lowest

Table 4 Limited asbestos exposure in housewives leading to mesothelioma

Interval between firstAge at death (yr) Work Duration of work (yr) exposure and death (yr) Asbestosfibre count

74 Sackware factory 1 60 287 00078 1 60 550 00059 2 30 300 00047 3 30 3 300 00055 Gasmask factory 5 30 57 000 00061 ,, 4 31 23 00000057 , 0-5 30 1700000069 0-5 35 1 600000

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570%o under 10000 fib29% over 20 000 f ib


smoking habits of patients with tumours of thecommoner cell-types. The overall frequency ofcigarette smoking in the series was 83%, 67% of

Ires per gram patients smoking over 15 cigarettes per day.,res pergrom None of the patients had a history of industrial

lung disease and routine histological sectionsshowed no asbestosis in any cases; only occasionalasbestos bodies were present.The asbestos-fibre content of the series is shown

in Fig. 3, and it is very similar to that of thecontrol series. Fifty-seven per cent of patientshad less than 10 000 fibres and 80% had less than20 000 fibres.The occupations and homes of the 10 patients

2 I with the lowest asbestos-fibre counts are shown in40 50 Table 7. All the occupations are traditional jobs

which do not involve the use of asbestos. Six ofcontrol series these patients had lived their lives in industrial

cities, although 22% of patients in the lung cancer

Table 5 Occupations and homes of 10 patients in control series with the lowest and highest asbestos fibrecounts

Low counts High countsNumber Job Number Job

O Tailoress 521 000 Docker0 Housewife 109 000 Joiner, french polisher0 Housewife 145 000 Merchant navy0 Grocer 285 000 Ship repairer0 Lorry driver 109 000 Painter, building site scaffolder0 Dance-hall manager, BTS driver 245 000 Bricklayer

1400 Tea inspector, medical orderly 103 000 Roof repairer2100 Office clerk 169 000 Coal merchant2400 Food packer in factory 76 500 Docker, merchant navy2600 Bookbinder 56 000 Fitter's labourer at chemical works

counts had little or no contact with asbestos atwork, whereas the 10 patients with the highestcounts were in occupations associated withasbestos exposure.

Pleural plaques were present in 55% of thepatients with over 20 000 fibres per gram, but inonly 5-5% of those with fewer fibres.

LUNG CANCER SERIESThe histological cell-types of the tumours in thisseries are shown in Table 6, together with the

Table 6 Cell type frequency and smoking habits oflung cancer patients

Frequency % Cigarette % Over 10Type ( Y.) smokers cigsper day

Squamous 52 88 73Oat-cell 16 87 62Adenocarcinoma and

malignant adenomatosis 17 76 59Carcinoma simplex 9Adenosquamous 4Giant-cell 2

14- 570/o under 10000 fibres perqram

200/o per gram

12 4

10'IU

4.

2.

0-0 4 8 12 16b20 30 40 54

Asbestos fibres per gram in thousands

Fig. 3 Asbestos fibre content of lung cancer series(9 highest not shown in figure).

series had lived in rural Wales, Cheshire, Lanca-shire or the Isle of Man.The occupations of the 10 patients with the

highest counts are shown in Table 8, and the jobsare similar to those of subjects with high counts

382

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Fig. 2 Asbestos fibre content of normal,(15 highest not shown in figure).

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Relationship between occupations and asbestos-fibre content of the luings

Table 7 Occupations and homes of the 10 patientswith the lowest asbestos fibre counts in lung cancerseries

No. Occupation Home

0 Butcher St. Helens0 Grocer LiverpoolO Agricultural worker Isle of ManO Butcher Liverpool0 Farmer Lancashire

800 Farmer North Wales1000 Tailor Liverpool1400 Housewife, school canteen worker St. Helens2000 Biscuit factory worker Liverpool2800 Housewife, laundry worker Queensferry

Table 8 Occupations of the 10 patients with thehighest asbestos fibre counts in lung cancer series

Number Occupation

115 000 Ship's carpenter107 000 Docker136 000 Roadsweeper151 000 Docker146 000 Property repairer, plasterer61 000 Ship repairyard labourer88 000 Sewer excavator and building site labourer61 000 Merchant service, atomic works construction55 000 Decorator, painter42 000 Docker

in the control series, and to those of patients inthe mesothelioma series who had had considerableexposure to asbestos, six of them in docks orshipyards.

Discussion

DOSE RELATIONSHIP BETWEEN ASBESTOS EXPOSUREAND MESOTHELIOMAStatements have often been made in news mediaand in the medical press suggesting that there isno dose relationship between asbestos exposureand mesothelioma, and this is probably a majorsource of alarm to the public, who have been toldthat nearly all adult lungs contain asbestos. Asrecently as 1976 a leading article in the Lancetstated that death from mesothelioma can followquite casual and short-term exposure to crocido-lite. In a search for the asbestos sources of 246confirmed mesotheliomas which had been re-corded in the British Mesothelioma Register in1967 and 1968, Greenberg and Davies (1974) in-cluded 14 cases which they called non-occupationalasbestos-induced mesotheliomas, where the actualasbestos exposure must in most cases have beenslight and often very brief. Wagner (1972) statedthat mesothelioma may follow brief, but notnecessarily light, asbestos exposure, and said thatthere did not appear to be any clear pattern of

dose response between asbestos exposure andmesothelioma. However, Newhouse (1973), fromstudies of asbestos factory workers, found thatthe mesothelioma rate increased with the severityand duration of asbestos exposure, and concludedthat the formation of asbestos-induced mesothe-lioma is dose related.The present study suggests a definite dose re-

lationship between the numbers of asbestos fibresseen in the patients' lungs and the presence ofasbestos-induced mesotheliomas. Ninety-five percent of the patients with asbestos-induced meso-theliomas had over 50 000 asbestos fibres per gramof dried lung in the base of a lower lobe, whereasonly 15% of the control series had as muchasbestos (Fig. 4). It is true that in many cases theasbestos exposure of mesothelioma patients hadbeen of short duration, sometimes only threemonths, but from the amount of asbestos fibresfound in these patients' lungs the exposure musthave been quite intense.The risk of asbestos-induced mesothelioma to

the general public, such as those in the controlseries, is probably confined to the top 15% re-ferred to above, which include no women andonly men working in jobs with a definite occu-pational hazard from inhaled asbestos.

SOURCE OF ASBESTOS IN ADULT URBAN LUNGSIn the control series, and in the lung cancer series,57% of the patients had up to 10000 asbestosfibres per gram of dried lung in the bases of theirlower lobes. This amount of asbestos is probablyharmless and may represent a background urbanlevel created by the widespread use of asbestos in

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Fig. 4 Comparison of asbestos fibre content of lungsfrom mesothelioma and normal control series.

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the last half century. Higher levels of asbestos inlungs appears to be derived mainly from theoccupations of the patients.

If urban asbestos pollution, severe enough tohave caused mesothelioma, can be derived fromliving in the vicinity of asbestos factories, docks,and shipyards, as suggested by Newhouse andThompson (1965) and Greenberg and Davies(1974), it would be expected that patients livingnear such areas would have high asbestos-fibrecounts. Although Merseyside has contained noasbestos factories, which may be the heaviestsource of atmospheric pollution, it contains manyshipyards and docks and sack-repair factories. Inthe lung cancer and control series there were 73patients who had lived the greater part of theirlives in one district of Merseyside. Figure 5 is amap of the conurbation on which is indicated bystippling the sites of shipyards, docks, and sack-repair factories. The sites of patients' homes areindicated, those with less than 10 000 fibres pergram of lung being scored differently from thosewith higher counts; where a high count is fullyexplained by the patients' jobs this is also shown.

0 Patients with under 10000fibres/qover * Is to

. over ,. .. ..and occupational asbestos exposure

Fig. 5 Map of Merseyside showing sites of expectedasbestos concentrations and the homes of patientswith high and low asbestos-fibre counts.

There is no concentration of high asbestoscount cases in the vicinity of docks and shipyards,or to the north-east of them, allowing for theprevailing wind. Most high count cases near thesuspect areas are fully explained by the jobs ofthe patients. In fact the map shows that shipyardworkers and dockers tend to live near their jobs.The four high count patients inland of the citywere dockers who, in later life, had moved to newhousing estates.

HOME-ENVIRONMENT ASBESTOS-INDUCEDMESOTHELIOMASEvidence supporting the existence of thesetumours is provided by Newhouse and Thompson(1965) and Greenberg and Davies (1974), the for-mer being a retrospective study of cases diagnosedin the London Hospital between 1917 and 1964,and the latter being an analysis of mesotheliomacases recorded by the Mesothelioma Panel in 1967and 1968.

Bohlig and Hain (1973) have laid down criteriafor acceptance of such tumours, including tumourhistology, asbestos exposure history, and quantita-tive evidence of asbestos exposure from examinedlung tissues. Few published cases meet these cri-teria, yet Bohlig and Hain do not emphasise theimportance of obtaining detailed occupationalhistories from living patients.

This point is illustrated by many patients whowere sack-repairers on Merseyside. The first twosuch cases were recorded by Owen in 1964, afurther four cases were described by Whitwell andRawcliffe in 1971, since when we have seen a fur-ther six patients, nearly all women. Since thebeginning of the century, until the practice waschanged quite recently, asbestos was importedinto Liverpool in hessian sacks for further trans-port to Rochdale. Damaged sacks were repaired insack-repair factories on Merseyside, where therewere a dozen such factories. Although this hazardhas been noted only on Merseyside, it is highlyprobable that asbestos was also shipped intoLondon docks in similar containers for transferto asbestos factories, and that damaged sacks wererepaired locally in sack-repair factories, whichwere numerous in London. The patients, or moreoften their relatives, who were questioned by New-house and Thompson, were asked about employ-ment in asbestos factories, not sack-repairfactories, so many of the cases described as home-environment mesothelioma may, in fact, havebeen sack repairers.Dependence upon relatives to provide industrial

histories of deceased patients is often unreliable.

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One of us (FW) has several times attended in-quests on cases of mesothelioma where close rela-tives knew nothing about the relevant occupationof the deceased, who sometimes had lived near thedocks. If the patients had not been interviewedabout jobs while in hospital usually months beforedeath, so that a true occupational history wasknown, the mesotheliomas might have been attri-buted to home-environment asbestos contamina-tion from the docks.Apart from the consideration of undisclosed

occupational hazards, the possibility of a meso-thelioma being a spontaneous tumour must beconsidered before it is accepted as being due tohome-environment asbestos contamination, andthis involves assessment of the asbestos fibre con-tent in the lungs, and the age of the patient. Manyspontaneous mesotheliomas occur in youngpatients, even children, as can be seen from astudy of the older literature. The actual age of thepatient may often be less than the usual inductionperiod of an asbestos-induced mesothelioma. Inthe present series only 7% of pleural meso-theliomas were thought to be spontaneous tu-mours, but this is much lower than their trueincidence in the community, as spontaneous meso-

theliomas are not always reported to the coroner.

Probably only around 15% of mesotheliomas are

spontaneous neoplasms at the present time on

Merseyside where there are many sources of oc-

cupational asbestos exposure.

'SUB-ASBESTOSIS' ASBESTOS EXPOSURE AND LUNGCANCERLung cancer occurring with asbestosis has beenknown since 1935 (Lynch and Smith, 1935) but theincidence of this complication has increasedgreatly, so that nowadays over half the patientswith asbestosis die from lung cancer (Buichanan,1965). The tumour is usually found in parts of thelung most severely affected by asbestosis, and it isnot clear whether the carcinoma is a reaction tothe asbestos itself or to the fibrosis caused by it.It is generally held that asbestos exposure leadsto lung cancer only when considerable asbestosisis present.However, studies in America on large numbers

of insulation workers, summarised by Selikoff etal. (1973) and Hammond and Selikoff (1973), sug-

gest that the incidence of lung cancer in asbestosworkers who do not have asbestosis is far higherthan the incidence in an unexposed population,and that this high rate of lung cancer is dependentupon the workers being cigarette smokers. It issaid that asbestos insulation workers with a history

of regular cigarette smoking have eight times therisk of lung cancer compared with smokers notexposed to asbestos. In the various series studiedthere have usually been about three times thenumber of deaths ascribed to lung cancer com-pared with asbestosis. In spite of the large numbersof patients in these series there have been veryfew necropsy confirmations of the diagnosis,which has been made largely from radiographsand death certificates. The only study of thepathology of these cases is that of Kannersteinand Churg (1972) based upon 33 necropsy and 11surgical specimens, many showing fibrosis andasbestos bodies as well as lung cancers, but theauthors saw no correlation between the numbersof asbestos bodies and lung fibrosis in the areasexamined.

If 'sub-asbestosis' asbestos exposure really in-creases the incidence of cigarette-induced lungcancer, as has been suggested, the lung tissues ofan urban series of lung cancer patients might beexpected to show higher concentrations of asbestosfibres than are present in a control series of lungsfrom a population of similar age and sex distribu-tion. It was to answer this question that thepresent series of lungs from lung cancer patientswas examined. The results show a very similarasbestos fibre content in the lungs of lung cancerpatients and of controls. In both series 57% ofpatients had less than 10 000 fibres and there werefewer patients in the cancer series than in thecontrol series with high counts.

This finding is the opposite of that reached byWarnock and Churg (1975), who compared thenumbers of asbestos bodies in 30 cancer lungs and100 control lungs, both series from an area of lowasbestos pollution, and found significantly moreasbestos bodies in the lung cancer series. Theyconcluded that even extremely low levels of asbe$-tos exposure may have a carcinogenic effect. How-ever, their two series were ifl-balanced, 77% ofthe cancer series but only 49% of the controlseries being men. The significant differences theyreported are fully explained by the known higherincidence and levels of asbestos bodies in malelungs.Our investigations into asbestos levels in the

lungs of lung cancer patients in the general popu-lation provides some assurance that urban asbestospollution does not contribute to the present highincidence of cigarette-induced lung cancer. How-ever, it does not provide an answer to the import-ant question whether asbestos workers can de-velop lung cancer from asbestos without firsthaving asbestosis. Such an answer can be found

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only after extensive necropsy studies incorporatingasbestos-fibre analysis.

We thank Drs W. B. Lister and A. N. Dempsey,senior medical officers to the Manchester Pneumo-coniosis Medical Panel, for their help in providingindustrial histories of mesothelioma patients, andMr S. R. Barter, HM Merseyside coroner, and hisstaff for obtaining histories of patients in thecontrol series. We acknowledge with gratitude thereceipt of a grant from the North West CancerResearch Fund to support this work.

References

Ashcroft, T., and Heppleston, A. G. (1973). Theoptical and electron microscopic determination ofpulmonary asbestos fibre concentration, and itsrelation to the human pathological reaction. Journalof Clinical Pathology, 26, 224-234.

Bohlig, H., and Hain, E. (1973). Cancer in relationto environmental exposure. In Biological Effects ofAsbestos, edited by P. Bogovski et al., pp. 217-221.International Agency for Research on Cancer,Lyons.

Buchanan, W. D. (1965). Asbestosis and primary intra-thoracic neoplasms. A nnals of the New YorkAcademy of Science, 132, 507-518.

Gold, C. (1968). The quantitation of asbestos in tissue(abstract). Journal of Clinical Pathology, 21, 537.

Greenberg, M., and Davies, T. A. L. (1974). Meso-thelioma Register 1967-68. British Journal ofInda-strial Medicine, 31, 91-104.

Hammond, E. C., and Selikoff, I. J. (1973). Relation ofcigarette smoking to risk of death of asbestos-associated disease among insulation workers in theUnited States. In Biological Effects of sbestos,edited by P. Bogovski et al.. pp. 312-317. Inter-national Agency for Research on Cancer, Lyons.

Kannerstein, M., and Churg, J. (1972). Pathology ofcarcinoma of the lung associated with asbestosexposure. Cancer, 30, 14-21.

Lancet (1976). Asbestos in the air. Leading article,Lancet, 1, 944-945.

Lynch, K. M., and Smith, W. A. (1935). Pulmonary

F. Whitwell, Jean Scott, and Myra Grimshawv

asbestosis III. Carcinoma of the lung in asbesto-silicosis. American Journal of Cancer, 24, 56-64.

Newhouse, M. L. (1973). Asbestos in the work placeand the community. Annals of Occupational Hy-giene, 16, 97-107.

Newhouse, M. L., and Thompson, H. (1965). Meso-thelioma of pleura and peritoneum following expo-sure to asbestos in the London area. British Journalof Industrial Medicine, 22, 261-269.

Owen, W. G. (1964). Diffuse mesothelioma and expo-sure to asbestos dust in the Merseyside area. BritishMedical Journal, 2, 214-218.

Selikoff, I. J., Hammond, E. C., and Seidman, H.(1973). Cancer risk of insulation workers in theUnited States. In Biological Effects of Asbestos,edited by P. Bogovski et al., pp. 209-216. The Inter-national Agency for Research on Cancer, Lyons.

Thomson, J. G., Kaschula, R. 0. C., and MacDonald,R. R. (1963). Asbestos as a mcdern urban hazard.South African Medical Journal, 37, 77-81.

Timbrell, V. (1973). Discussion Summary. In Biologi-cal Effects of Asbestos, edited by P. Bogovski et al.,p. 131. The International Agency for Research onCancer, Lyons.

Utidjian, M. D., Gross, P., and deTreville, R. T. P.(1968). Ferruginous bodies in human lungs. Pre-valence at random autopsies. Archives of Environ-mental Health, 17, 327-333.

Wagner, J. C. (1972). Current cpinions on the asbestoscancer problem. Annals of Occupational Hygiene,15, 61-64.

Wagner, J. C., Sieggs, C. A., and Marchand, P. (1960).Diffuse pleural mesothelioma and asbestos exposurein the North Western Cape Province. British Journalof Industrial Medicine, 17, 260-271.

Warnock, M. L., and Churg, A. M. (1975). Associa-tion of asbestos and bronchogenic carcinoma in apopulation with low asbestos exposure. Cancer(Philadelphia), 35, 1236-1242.

Whitwell, F., and Rawcliffe, R. M. (1971). Diffusemalignant pleural mesothelioma and asbestos ex-posure. Thorax, 26, 6-22.

Requests for reprints to: Dr F. Whitwell, Departmentof Pathology, Broadgreen Hospital, Thomas Drive,Liverpool L14 3LB.



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Relationship and contentRelationship betweenoccupationsandasbestos-fibre contentof thelungs Merseyside hospitals, and 45 patients were from other parts of north-west England. Normal